The major objective of this project is to relate age dependent changes in the biochemistry of the lens to the development of senile cataract. It is a basic premise of this proposal that senile cataract characterized by central opacity may be caused by aspects of the aging process. The approach to be pursued is based upon our previous observations. Five fundamental lines of investigation will be pursued. 1. To elucidate age dependent changes in the physical and chemical structure of the structural lens proteins and compare them with altered protein macromolecules of the cataractous lens. 2. To elucidate the chemistry of the non-tryptophan fluorescent components and the yellowing of lens which appears to develop with aging and is localized primarily in the nucleus region. 3. To explain the age dependent increase in the so-called insoluble protein fraction. Does it arise primarily from the high molecular weight fraction or by other routes? Is it associated with the development of senile cataract? 4. To study age dependent changes in protein synthesis, nucleic acid metabolism and their possible relationship to cataract formation. 5. To ascertain if either limited or exhaustive proteolytic activity increases with aging or in the senile cataractous lens.